Laminin receptor (67 LR) is a 67 kDa protein derived from a 37 kDa precursor (37LR). 37/67 LR is a strong clinical correlate for progression, aggression, and chemotherapeutic relapse of several cancers including breast, prostate, and colon. The ability of 37/67 LR to promote cancer cell aggressiveness is further increased by its ability to transduce physiochemical and mechanosensing signals in endothelial cells and modulate angiogenesis. Recently, it was demonstrated that 37/67 LR modulates the anti-angiogenic potential of the secreted glycoprotein pigment epithelium-derived factor (PEDF).
In silico (literally Latin for “in silicon”, alluding to the mass use of silicon for semiconductor computer chips) is an expression used to mean “performed on computer or via computer simulation.” The phrase was coined as an allusion to the Latin phrases in vivo, in vitro, and in situ, which are commonly used in biology and refer to experiments done in living organisms, outside of living organisms, and where they are found in nature, respectively.
In silico study in medicine is thought to have the potential to speed the rate of discovery while reducing the need for expensive lab work and clinical trials. One way to achieve this is by producing and screening drug candidates more effectively. In 2010, for example, using the protein docking algorithm EADock (see Protein-ligand docking), researchers found potential inhibitors to an enzyme associated with cancer activity in silico. Fifty percent of the molecules were later shown to be active inhibitors in vitro. This approach differs from use of expensive high-throughput screening (HTS) robotic labs to physically test thousands of diverse compounds a day often with an expected hit rate on the order of 1% or less with still fewer expected to be real leads following further testing.
Osteoarthritis affects over 27 million Americans age 25 and older and is a debilitating disease in which articular cartilage degradation leads to inflammation and pain in the joint. Medical management has not been very successful, as cartilage is avascular and has a difficult time regenerating itself. In joints, when PEDF (pigment epithelial derived factor) bind to laminin receptors (LR), it has anti-inflammatory, pro-chondrogenic and anti-angiogenic characteristics. However, the relatively large size and low stability of PEDF at 25° C. indicates that smaller, more stable molecules could be an alternative for therapeutic purposes. Thus, there is a need to identify smaller, more stable molecules for these therapeutic purposes.